Hex: a homeobox gene revealing peri-implantation asymmetry in the mouse embryo and an early transient marker of endothelial cell precursors
Abstract
The divergent homeobox gene Hex exhibits three notable expression patterns during early mouse development. Initially Hex is expressed in the primitive endoderm of the implanting blastocyst but by 5.5 dpc its transcripts are present only in a small patch of visceral endoderm at the distal tip of the egg cylinder. Lineage analysis shows that these cells move unilaterally to assume an anterior position while continuing to express Hex. The primitive streak forms on the opposite side of the egg cylinder from this anterior Hex expression domain approximately 24 hours after the initial anterior movement of the distal visceral endoderm. Thus, Hex expression marks the earliest unequivocal molecular anteroposterior asymmetry in the mouse embryo and indicates that the anteroposterior axis of the embryo develops from conversion of a proximodistal asymmetry established in the primitive endoderm lineage. Subsequently, Hex is expressed in the earliest definitive endoderm to emerge from the streak and its expression within the gut strongly suggests that the ventral foregut is derived from the most anterior definitive endoderm and that the liver is probably the most anterior gut derivative. Hex is also an early marker of the thyroid primordium. Within the mesoderm, Hex is transiently expressed in the nascent blood islands of the visceral yolk sac and later in embryonic angioblasts and endocardium. Comparison with flk-1 (T. P. Yamaguchi et al., Development 118, 489-498, 1993) expression indica…
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Day-3 hPSC-derived posterior foregut expressed HHEX, a marker of ∼E8.5 mouse ventral posterior foregut.
“Such day-3 hPSC-derived posterior foregut expressed HHEX (Figure S1H), a marker of ∼E8.5 mouse ventral posterior foregut (Thomas et al., 1998).”
From A Roadmap for Human Liver Differentiation from Pluripotent Stem Cells (2018) · cites this paper as Thomas et al., 1998
EPI descendants resembled embryonic VE (emVE) and anterior visceral endoderm (AVE), based on expression of markers including Lefty1, Cer1 and Hhex.
“Expression of markers of embryonic (em)VE, and anterior visceral endoderm (AVE), a specialized cellular cohort of emVE exhibiting an intra-epithelial, distal-to-anterior migratory behavior between E5.5 and E6.0, including Lefty1, Cer1 and Hhex30–32, suggested these EPI descendants resembled emVE and AVE (Fig. 2c, Extended Data Fig. 6e)33.”
From The emergent landscape of the mouse gut endoderm at single-cell resolution (2019) · cites this paper as [30]
emVE-specific genes include Lhx1 and Lefty1, and AVE-specific genes include Cer1 and Hhex; exVE-specific genes include Apln and Msx1.
“emVE-specific genes (Fig. 3c, Cluster 1) included Lhx1 and Lefty1, and AVE-specific genes Cer1 and Hhex30,32,37. ExVE-specific genes (Fig. 3c, Cluster 2) included Apln and Msx1 (Supplementary Table 4).”
From The emergent landscape of the mouse gut endoderm at single-cell resolution (2019) · cites this paper as [30]
Hhex was missed in the authors' analysis because it was expressed in 67 of their SAGE libraries and thus did not fit their criteria for validation lists.
“Furthermore, the foregut marker, Hhex, was missed in our analysis since it was expressed in 67 of our SAGE libraries, and thus did not fit our criteria for our validation lists (Table 1 and Additional file 2) [44].”
From A systematic screen for genes expressed in definitive endoderm by Serial Analysis of Gene Expression (SAGE) (2007) · cites this paper as [44]
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References 67 · Cited by 528
- Authors
- Thomas, P. Q., Brown, A., & Beddington, R. S. P.
- Affiliations
- National Institute for Medical Research (GB)
- Institute of Cancer Research (GB)
- Corresponding author
- Brown, A.
- Beddington, R. S. P.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 1998-01-01
- Volume
- 125
- Issue
- 1
- Pages
- 85-94
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2108946209
- Cited by
- 528
- References
- 67
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 12 · 2023: 10 · 2022: 4 · 2021: 14 · 2020: 10 · 2019: 8 · 2018: 12 · 2017: 13 · 2016: 14 · 2015: 12 · 2014: 8 · 2013: 15 · 2012: 17
- FWCI
- 12.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Renal and related cancers
- Keywords
- anterior-posterior axis, visceral endoderm, primitive endoderm, egg cylinder, primitive streak, definitive endoderm, foregut, endothelial precursors, Flk-1, yolk sac blood islands, endocardium, mouse embryo
- MeSH terms
- Animals, Carbocyanines, Cell Differentiation, Digestive System, Embryo, Mammalian, Endoderm, Endothelium, Vascular, Embryonic and Fetal Development, Gastrula, Genes, Homeobox, Histocytochemistry, RNA, Messenger, Stem Cells, Transcription Factors, In Situ Hybridization, Receptors, Growth Factor, Homeodomain Proteins, Gene Expression Regulation, Developmental, Neovascularization, Physiologic, Body Patterning, Receptor Protein-Tyrosine Kinases, Receptors, Vascular Endothelial Growth Factor, Mice
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